This is a randomized, double-blinded, placebo-controlled evaluation of the prophylactic antimalarial activity of atovaquone. The dosing regimens include atovaquone 750 mg x 7 (6 subjects); atovaquone 250 mg x 1 (6 subjects); and placebo (4 subjects). The study has been conducted largely on an outpatient basis. Starting September 30, sixteen eligible volunteers received seven daily doses of atovaquone/placebo and were challenged on the second day with Plasmodium falciparum (by the bite of five infected mosquitoes). They were then monitored daily (for 21 days), every other day (for two weeks), and weekly (until 12 weeks after challenge), for evidence of patent malaria. Four volunteers developed patent malaria and were successfully treated with chloroquine. The other 12 have remained parasite-free. Fifteen of the volunteers have complied 100% with the outpatient follow-up regimen. However, on two occasions during this period, one of the volunteers found it difficult to come to the clinic. To ensure his safety, he agreed to be admitted to the inpatient GCRC unit, where he was monitored reliably for 54 days.